Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known a...Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in goats.Therefore,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.Results For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression signatures.Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system,oxidative phosphorylation,and apoptosis.Subsequently,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of GCs.Additionally,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.Conclusions This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell typespecific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.展开更多
Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we...Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.展开更多
The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates ...The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined.This study provides the first comprehensive,unbiased,cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens.Within the hypothalamus,pituitary,and ovary,seven,12,and 13 distinct cell types were identified,respectively.Results indicated that the pituitary adenylate cyclase activating polypeptide(PACAP),follicle-stimulating hormone(FSH),and prolactin(PRL)signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone(GnRH),FSH,and luteinizing hormone(LH)within the hypothalamus and pituitary.In the ovary,interactions between granulosa cells and oocytes involved the KIT,CD99,LIFR,FN1,and ANGPTL signaling pathways,which collectively regulate follicular maturation.The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis.Additionally,gene expression analysis revealed that relaxin 3(RLN3),gastrin-releasing peptide(GRP),and cocaine-and amphetamine regulated transcripts(CART,also known as CARTPT)may function as novel endocrine hormones,influencing the HPO axis through autocrine,paracrine,and endocrine pathways.Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP,RLN3,CARTPT,LHCGR,FSHR,and GRPR in the ovaries of Lohmann layers,potentially contributing to their superior reproductive performance.In conclusion,this study provides a detailed molecular characterization of the HPO axis,offering novel insights into the regulatory mechanisms underlying reproductive biology.展开更多
Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered ...Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.展开更多
Background In the modern sheep production systems,the reproductive performance of ewes determines the economic profitability of farming.Revealing the genetic mechanisms underlying differences in the litter size is imp...Background In the modern sheep production systems,the reproductive performance of ewes determines the economic profitability of farming.Revealing the genetic mechanisms underlying differences in the litter size is important for the selection and breeding of highly prolific ewes.Hu sheep,a high-quality Chinese sheep breed,is known for its high fecundity and is often used as a model to study prolificacy traits.In the current study,animals were divided into two groups according to their delivery rates in three consecutive lambing seasons(namely,the high and low reproductive groups with≥3 lambs and one lamb per season,n=3,respectively).The ewes were slaughtered within 12 h of estrus,and unilateral ovarian tissues were collected and analyzed by 10×Genomics single-cell RNA sequencing.Results A total of 5 types of somatic cells were identified and corresponding expression profiles were mapped in the ovaries of each group.Noticeably,the differences in the ovary somatic cell expression profiles between the high and low reproductive groups were mainly clustered in the granulosa cells.Furthermore,four granulosa cell subtypes were identified.GeneSwitches analysis revealed that the abundance of JPH1 expression and the reduction of LOC101112291 expression could lead to different evolutionary directions of the granulosa cells.Additionally,the expression levels of FTH1 and FTL in mural granulosa cells of the highly reproductive group were significantly higher.These genes inhibit necroptosis and ferroptosis of mural granulosa cells,which helps prevent follicular atresia.Conclusions This study provides insights into the molecular mechanisms underlying the high fecundity of Hu sheep.The differences in gene expression profiles,particularly in the granulosa cells,suggest that these cells play a critical role in female prolificacy.The findings also highlight the importance of genes such as JPH1,LOC101112291,FTH1,and FTL in regulating granulosa cell function and follicular development.展开更多
Carbazole moiety-based 2PACz([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)self-assembled monolayers(SAMs)are excellent hole-selective contact(HSC)materials with abilities to excel the charge-transferdynamics of perovski...Carbazole moiety-based 2PACz([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)self-assembled monolayers(SAMs)are excellent hole-selective contact(HSC)materials with abilities to excel the charge-transferdynamics of perovskite solar cells(PSCs).Herein,we report a facile but powerful method to functionalize the surface of 2PACz-SAM,by which reproducible,highly stable,high-efficiency wide-bandgap PSCs can be obtained.The 2PACz surface treatment with various donor number solvents improves assembly of 2PACz-SAM and leave residual surface-bound solvent molecules on 2PACz-SAM,which increases perovskite grain size,retards halide segregation,and accelerates hole extraction.The surface functionalization achieves a high power conversion efficiency(PCE)of 17.62%for a single-junction wide-bandgap(~1.77 e V)PSC.We also demonstrate a monolithic all-perovskite tandem solar cell using surfaceengineered HSC,showing high PCE of 24.66%with large open-circuit voltage of 2.008 V and high fillfactor of 81.45%.Our results suggest this simple approach can further improve the tandem device,when coupled with a high-performance narrow-bandgap sub-cell.展开更多
Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding ...Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.展开更多
With the development of wireless communication technology,an urgent problem to be solved is co-site broadband interference on independent communication platforms such as satellites,space stations,aircrafts and ships.A...With the development of wireless communication technology,an urgent problem to be solved is co-site broadband interference on independent communication platforms such as satellites,space stations,aircrafts and ships.Also,the problem of strong selfinterference rejection should be solved in the co-time co-frequency full duplex mode which realizes spectrum multiplication in 5G communication technology.In the research of such interference rejection,interference cancellation technology has been applied.In order to reject multipath interference,multitap double LMS(Least Mean Square)loop interference cancellation system is often used for cancelling RF(Radio Frequency)domain interference cancelling.However,more taps will lead to a more complex structure of the cancellation system.A novel tap single LMS loop adaptive interference cancellation system was proposed to improve the system compactness and reduce the cost.In addition,a mathematical model was built for the proposed cancellation system,the correlation function of CP2FSK(Continuous Phase Binary Frequency Shift Keying)signal was derived,and the quantitative relationship was established between the correlation function and the interference signal bandwidth and tap delay differential.The steadystate weights and the expression of the average interference cancellation ratio(ICR)were deduced in the scenes of LOS(Line of Sight)interference with antenna swaying on an independent communication platform and indoor multipath interference.The quantitative relationship was deeply analyzed between the interference cancellation performance and the parameters such as antenna swing,LMS loop gain,and interference signal bandwidth,which was verified by simulation experiment.And the performance of the proposed interference cancellation system was compared with that of the traditional double LMS loop cancellation system.The results showed that the compact single LMS loop cancellation system can achieve an average interference rejection capability comparable to the double LMS loop cancellation system.展开更多
High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat ...High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.展开更多
Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer...Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.展开更多
Single incision laparoscopic liver resection(SILLR)is the most recent develop-ment in the laparoscopic approach to the liver.SILLR for hepatocellular carci-noma(HCC)has developed much more slowly than multiport LLR.So...Single incision laparoscopic liver resection(SILLR)is the most recent develop-ment in the laparoscopic approach to the liver.SILLR for hepatocellular carci-noma(HCC)has developed much more slowly than multiport LLR.So far,195 patients completed SILLR for HCC.In this paper,we reviewed all published papers about SILLR for HCC and discussed the feasibility of the SILLR,peri and postoperative findings,tricks of patient selection and whether SILLR compromise the oncological principles.展开更多
Spermatogenic cell heterogeneity is determined by the complex process of spermatogenesis differentiation.However,effectively revealing the regulatory mechanisms underlying mammalian spermatogenic cell development and ...Spermatogenic cell heterogeneity is determined by the complex process of spermatogenesis differentiation.However,effectively revealing the regulatory mechanisms underlying mammalian spermatogenic cell development and differentiation via traditional methods is difficult.Advances in technology have led to the emergence of many single-cell transcriptome sequencing protocols,which have partially addressed these challenges.In this review,we detail the principles of 10x Genomics technology and summarize the methods for downstream analysis of single-cell transcriptome sequencing data.Furthermore,we explore the role of single-cell transcriptome sequencing in revealing the heterogeneity of testicular ecological niche cells,delineating the establishment and disruption of testicular immune homeostasis during human spermatogenesis,investigating abnormal spermatogenesis in humans,and,ultimately,elucidating the molecular evolution of mammalian spermatogenesis.展开更多
Stem cells have shown great application potential in wound repair,tissue regeneration,and disease treatment.Therefore,a full understanding of stem cells and their related regulatory mechanisms in disease treatment is ...Stem cells have shown great application potential in wound repair,tissue regeneration,and disease treatment.Therefore,a full understanding of stem cells and their related regulatory mechanisms in disease treatment is conducive to improving the therapeutic effect of stem cells.However,thus far,there are still many unsolved mysteries in thefield of stem cells due to technical limitations,which hinder the in-depth exploration of stem cells and their wide clinical application.Single-cell sequencing(SCS)has provided very powerful and unbiased insights into cell gene expression profiles at the single-cell level,bringing exciting results to the stem cellfield.At present,SCS has been widely applied in thefield of stem cells,covering various aspects,including lineage tracing the development of stem cells,identifying new stem cell types,exploring cellular heterogeneity,and identifying internal functional subpopulations.In this paper,we focus on the latest research progress and discuss the application of SCS technology in stem cells.展开更多
Advances in chimeric antigen receptor(CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies.However,progress is still hindered as clinical b...Advances in chimeric antigen receptor(CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies.However,progress is still hindered as clinical benefit is only available for a fraction of patients.A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice.Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design,guide gene-based T cell modification,and optimize the CAR-T manufacturing conditions,and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes.The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities.In this review,we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies.We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy.Specifically,we provide an overview of single-cell studies focusing on target antigens,CAR-transgene integration,and preclinical research and clinical applications,and then discuss how it will affect the future of CAR-T cell therapy.展开更多
Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved ...Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.展开更多
BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing t...BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.展开更多
Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data...Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.展开更多
Fe-N-doped carbon materials(Fe-N-C)are promising candidates for oxygen reduction reaction(ORR)relative to Pt-based catalysts in proton exchange membrane fuel cells(PEMFCs).However,the intrinsic contributions of Fe-N_(...Fe-N-doped carbon materials(Fe-N-C)are promising candidates for oxygen reduction reaction(ORR)relative to Pt-based catalysts in proton exchange membrane fuel cells(PEMFCs).However,the intrinsic contributions of Fe-N_(4)moiety with different chemical/spin states(e.g.D1,D2,D3)to ORR are unclear since various states coexist inevitably.In the present work,Fe-N-C core-shell nanocatalyst with single lowspin Fe(Ⅱ)-N_(4)species(D1)is synthesized and identified with ex-situ ultralow temperature Mossbauer spectroscopy(T=1.6 K)that could essentially differentiate various Fe-N_(4)states and invisible Fe-O species.By quantifying with CO-pulse chemisorption,site density and turnover frequency of Fe-N-C catalysts reach 2.4×10^(-9)site g^(-1)and 23 e site~(-1)s^(-1)during the ORR,respectively.Half-wave potential(0.915V_(RHE))of the Fe-N-C catalyst is more positive(approximately 54 mV)than that of Pt/C.Moreover,we observe that the performance of PEMFCs on Fe-N-C almost achieves the 2025 target of the US Department of Energy by demonstrating a current density of 1.037 A cm^(-2)combined with the peak power density of 0,685 W cm^(-2),suggesting the critical role of Fe(Ⅱ)-N_(4)site(D1).After 500 h of running,PEMFCs still deliver a power density of 1.26 W cm^(-2)at 1.0 bar H_(2)-O_(2),An unexpected rate-determining step is figured out by isotopic labelling experiment and theoretical calculation.This work not only offers valuable insights regarding the intrinsic contribution of Fe-N_(4)with a single spin state to alkaline/acidic ORR,but also provides great opportunities for developing high-performance stable PEMFCs.展开更多
Traditional methods for measuring single-cell mechanical characteristics face several challenges,including lengthy measurement times,low throughput,and a requirement for advanced technical skills.To overcome these cha...Traditional methods for measuring single-cell mechanical characteristics face several challenges,including lengthy measurement times,low throughput,and a requirement for advanced technical skills.To overcome these challenges,a novel machine learning(ML)approach is implemented based on the convolutional neural networks(CNNs),aiming at predicting cells'elastic modulus and constitutive equations from their deformations while passing through micro-constriction channels.In the present study,the computational fluid dynamics technology is used to generate a dataset within the range of the cell elastic modulus,incorporating three widely-used constitutive models that characterize the cellular mechanical behavior,i.e.,the Mooney-Rivlin(M-R),Neo-Hookean(N-H),and Kelvin-Voigt(K-V)models.Utilizing this dataset,a multi-input convolutional neural network(MI-CNN)algorithm is developed by incorporating cellular deformation data as well as the time and positional information.This approach accurately predicts the cell elastic modulus,with a coefficient of determination R^(2)of 0.999,a root mean square error of 0.218,and a mean absolute percentage error of 1.089%.The model consistently achieves high-precision predictions of the cellular elastic modulus with a maximum R^(2)of 0.99,even when the stochastic noise is added to the simulated data.One significant feature of the present model is that it has the ability to effectively classify the three types of constitutive equations we applied.The model accurately and reliably predicts single-cell mechanical properties,showcasing a robust ability to generalize.We demonstrate that incorporating deformation features at multiple time points can enhance the algorithm's accuracy and generalization.This algorithm presents a possibility for high-throughput,highly automated,real-time,and precise characterization of single-cell mechanical properties.展开更多
基金supported by the National Key Research and Development Program of China(2022YFD1300202)the Technology Innovation and Application Development Special Project of Chongqing(cstc2021jscx-gksb X0008)+2 种基金the National Natural Science Foundation of China(32102623)the National Natural Science Foundation of Chongqing(cstc2021jcyj-msxm X0875)the Ph D Train Scientific Research Project of Chongqing(CSTB2022BSXM-JCX0002)。
文摘Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in goats.Therefore,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.Results For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression signatures.Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system,oxidative phosphorylation,and apoptosis.Subsequently,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of GCs.Additionally,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.Conclusions This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell typespecific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.
基金supported by the National Natural Science Foundation of China (No.32070656)the Nanjing University Deng Feng Scholars Program+1 种基金the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions,China Postdoctoral Science Foundation funded project (No.2022M711563)Jiangsu Funding Program for Excellent Postdoctoral Talent (No.2022ZB50)
文摘Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.
基金supported by the Natural Science Foundation of Sichuan Province(2022NSFSC1767)National Natural Science Foundation of China(32360828)。
文摘The hypothalamic-pituitary-ovarian(HPO)axis represents a central neuroendocrine network essential for reproductive function.Despite its critical role,the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined.This study provides the first comprehensive,unbiased,cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens.Within the hypothalamus,pituitary,and ovary,seven,12,and 13 distinct cell types were identified,respectively.Results indicated that the pituitary adenylate cyclase activating polypeptide(PACAP),follicle-stimulating hormone(FSH),and prolactin(PRL)signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone(GnRH),FSH,and luteinizing hormone(LH)within the hypothalamus and pituitary.In the ovary,interactions between granulosa cells and oocytes involved the KIT,CD99,LIFR,FN1,and ANGPTL signaling pathways,which collectively regulate follicular maturation.The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis.Additionally,gene expression analysis revealed that relaxin 3(RLN3),gastrin-releasing peptide(GRP),and cocaine-and amphetamine regulated transcripts(CART,also known as CARTPT)may function as novel endocrine hormones,influencing the HPO axis through autocrine,paracrine,and endocrine pathways.Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP,RLN3,CARTPT,LHCGR,FSHR,and GRPR in the ovaries of Lohmann layers,potentially contributing to their superior reproductive performance.In conclusion,this study provides a detailed molecular characterization of the HPO axis,offering novel insights into the regulatory mechanisms underlying reproductive biology.
基金partially supported by the Natural Science Foundation of Zhejiang Province(Award number:D21C170001)the National Natural Science Foundation of China(Award number:31973000)。
文摘Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.
基金supported by the mutton sheep industry technology system construction project of Shaanxi Province(NYKJ-2021-YL(XN)43).
文摘Background In the modern sheep production systems,the reproductive performance of ewes determines the economic profitability of farming.Revealing the genetic mechanisms underlying differences in the litter size is important for the selection and breeding of highly prolific ewes.Hu sheep,a high-quality Chinese sheep breed,is known for its high fecundity and is often used as a model to study prolificacy traits.In the current study,animals were divided into two groups according to their delivery rates in three consecutive lambing seasons(namely,the high and low reproductive groups with≥3 lambs and one lamb per season,n=3,respectively).The ewes were slaughtered within 12 h of estrus,and unilateral ovarian tissues were collected and analyzed by 10×Genomics single-cell RNA sequencing.Results A total of 5 types of somatic cells were identified and corresponding expression profiles were mapped in the ovaries of each group.Noticeably,the differences in the ovary somatic cell expression profiles between the high and low reproductive groups were mainly clustered in the granulosa cells.Furthermore,four granulosa cell subtypes were identified.GeneSwitches analysis revealed that the abundance of JPH1 expression and the reduction of LOC101112291 expression could lead to different evolutionary directions of the granulosa cells.Additionally,the expression levels of FTH1 and FTL in mural granulosa cells of the highly reproductive group were significantly higher.These genes inhibit necroptosis and ferroptosis of mural granulosa cells,which helps prevent follicular atresia.Conclusions This study provides insights into the molecular mechanisms underlying the high fecundity of Hu sheep.The differences in gene expression profiles,particularly in the granulosa cells,suggest that these cells play a critical role in female prolificacy.The findings also highlight the importance of genes such as JPH1,LOC101112291,FTH1,and FTL in regulating granulosa cell function and follicular development.
基金supported by the National Research Foundation of Korea (NRF)the Ministry of Science,ICT (2022M3J1A1085285,2019R1A2C1084010,and 2022R1A2C2006532)the Korea Electric Power Corporation (R20XO02-1)。
文摘Carbazole moiety-based 2PACz([2-(9H-carbazol-9-yl)ethyl]phosphonic acid)self-assembled monolayers(SAMs)are excellent hole-selective contact(HSC)materials with abilities to excel the charge-transferdynamics of perovskite solar cells(PSCs).Herein,we report a facile but powerful method to functionalize the surface of 2PACz-SAM,by which reproducible,highly stable,high-efficiency wide-bandgap PSCs can be obtained.The 2PACz surface treatment with various donor number solvents improves assembly of 2PACz-SAM and leave residual surface-bound solvent molecules on 2PACz-SAM,which increases perovskite grain size,retards halide segregation,and accelerates hole extraction.The surface functionalization achieves a high power conversion efficiency(PCE)of 17.62%for a single-junction wide-bandgap(~1.77 e V)PSC.We also demonstrate a monolithic all-perovskite tandem solar cell using surfaceengineered HSC,showing high PCE of 24.66%with large open-circuit voltage of 2.008 V and high fillfactor of 81.45%.Our results suggest this simple approach can further improve the tandem device,when coupled with a high-performance narrow-bandgap sub-cell.
基金Supported by Shenzhen Science and Technology Program,No.GJHZ20210705142543019Guangdong Basic and Applied Basic Research Foundation,No.2023A1515220074.
文摘Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.
基金supported by the National Natural Science Foundation of China[Grant No.61771187]the Natural Science Foundation of Hubei Province[Grant No.2016CFB396]+1 种基金the Hubei Provincial Technology Innovation Special Major Project[Grant No.2019AAA018]the Major Project of Hubei Collaborative Innovation Center for High-efficiency Utilization of Solar Energy[HBSKFZD2015002]。
文摘With the development of wireless communication technology,an urgent problem to be solved is co-site broadband interference on independent communication platforms such as satellites,space stations,aircrafts and ships.Also,the problem of strong selfinterference rejection should be solved in the co-time co-frequency full duplex mode which realizes spectrum multiplication in 5G communication technology.In the research of such interference rejection,interference cancellation technology has been applied.In order to reject multipath interference,multitap double LMS(Least Mean Square)loop interference cancellation system is often used for cancelling RF(Radio Frequency)domain interference cancelling.However,more taps will lead to a more complex structure of the cancellation system.A novel tap single LMS loop adaptive interference cancellation system was proposed to improve the system compactness and reduce the cost.In addition,a mathematical model was built for the proposed cancellation system,the correlation function of CP2FSK(Continuous Phase Binary Frequency Shift Keying)signal was derived,and the quantitative relationship was established between the correlation function and the interference signal bandwidth and tap delay differential.The steadystate weights and the expression of the average interference cancellation ratio(ICR)were deduced in the scenes of LOS(Line of Sight)interference with antenna swaying on an independent communication platform and indoor multipath interference.The quantitative relationship was deeply analyzed between the interference cancellation performance and the parameters such as antenna swing,LMS loop gain,and interference signal bandwidth,which was verified by simulation experiment.And the performance of the proposed interference cancellation system was compared with that of the traditional double LMS loop cancellation system.The results showed that the compact single LMS loop cancellation system can achieve an average interference rejection capability comparable to the double LMS loop cancellation system.
基金supported by the National Natural Science Foundation of China,No.82371051(to DW)the Natural Science Foundation of Beijing,No.7212092(to DW)+1 种基金the Capital’s Funds for Health Improvement and Research,No.2022-2-5041(to DW)the Fund of Science and Technology Development of Beijing Rehabilitation Hospital,Capital Medical University,No.2021R-001(to YL).
文摘High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.
基金funded by Young Elite Scientists Sponsorship Program by Beijing Association for science and technology(Grant No.BYESS2023226)。
文摘Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.
文摘Single incision laparoscopic liver resection(SILLR)is the most recent develop-ment in the laparoscopic approach to the liver.SILLR for hepatocellular carci-noma(HCC)has developed much more slowly than multiport LLR.So far,195 patients completed SILLR for HCC.In this paper,we reviewed all published papers about SILLR for HCC and discussed the feasibility of the SILLR,peri and postoperative findings,tricks of patient selection and whether SILLR compromise the oncological principles.
基金supported by National Key Research and Development Program of China(2022YFD1302201,2023YFF1000904)the National Natural Science Foundation of China(32072806,32372970)+2 种基金Key Technologies Demonstration of Animal Husbandry in Shaanxi Province(20221086,20230978)Inner Mongolia Autonomous Region Competition Leaders(2022JBGS0025)Xinjian Ugur Autonouous Region Scientific Research and Innovation Platform Construction Project“State Key Laboratory of Genetic Improvement and Germplasm”。
文摘Spermatogenic cell heterogeneity is determined by the complex process of spermatogenesis differentiation.However,effectively revealing the regulatory mechanisms underlying mammalian spermatogenic cell development and differentiation via traditional methods is difficult.Advances in technology have led to the emergence of many single-cell transcriptome sequencing protocols,which have partially addressed these challenges.In this review,we detail the principles of 10x Genomics technology and summarize the methods for downstream analysis of single-cell transcriptome sequencing data.Furthermore,we explore the role of single-cell transcriptome sequencing in revealing the heterogeneity of testicular ecological niche cells,delineating the establishment and disruption of testicular immune homeostasis during human spermatogenesis,investigating abnormal spermatogenesis in humans,and,ultimately,elucidating the molecular evolution of mammalian spermatogenesis.
文摘Stem cells have shown great application potential in wound repair,tissue regeneration,and disease treatment.Therefore,a full understanding of stem cells and their related regulatory mechanisms in disease treatment is conducive to improving the therapeutic effect of stem cells.However,thus far,there are still many unsolved mysteries in thefield of stem cells due to technical limitations,which hinder the in-depth exploration of stem cells and their wide clinical application.Single-cell sequencing(SCS)has provided very powerful and unbiased insights into cell gene expression profiles at the single-cell level,bringing exciting results to the stem cellfield.At present,SCS has been widely applied in thefield of stem cells,covering various aspects,including lineage tracing the development of stem cells,identifying new stem cell types,exploring cellular heterogeneity,and identifying internal functional subpopulations.In this paper,we focus on the latest research progress and discuss the application of SCS technology in stem cells.
基金National Key Research and Development Program of China(2022YFC2502700)National Natural Science Foundation of China(8187343482100190).
文摘Advances in chimeric antigen receptor(CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies.However,progress is still hindered as clinical benefit is only available for a fraction of patients.A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice.Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design,guide gene-based T cell modification,and optimize the CAR-T manufacturing conditions,and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes.The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities.In this review,we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies.We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy.Specifically,we provide an overview of single-cell studies focusing on target antigens,CAR-transgene integration,and preclinical research and clinical applications,and then discuss how it will affect the future of CAR-T cell therapy.
文摘Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.
文摘BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.
基金supported by the National Innovation and Enterpreneurship Training Program for College Students(202210367002)the Key Laboratory Open Project of An-hui Province(AHCM2022Z004).
文摘Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.
基金financial support from the“Hundred Talents Program”of the Chinese Academy of Sciencesthe“Young Talents Training Program”of the Shanghai Branch of the Chinese Academy of Sciences+3 种基金the financial support from the Xiamen City Natural Science Foundation of China(3502Z20227085,3502Z20227256)the National Science Youth Foundation of China(22202205)the Fujian Provincial Natural Science Foundation of China(2022J01502)Open Source Foundation of State Key Laboratory of Structural Chemistry。
文摘Fe-N-doped carbon materials(Fe-N-C)are promising candidates for oxygen reduction reaction(ORR)relative to Pt-based catalysts in proton exchange membrane fuel cells(PEMFCs).However,the intrinsic contributions of Fe-N_(4)moiety with different chemical/spin states(e.g.D1,D2,D3)to ORR are unclear since various states coexist inevitably.In the present work,Fe-N-C core-shell nanocatalyst with single lowspin Fe(Ⅱ)-N_(4)species(D1)is synthesized and identified with ex-situ ultralow temperature Mossbauer spectroscopy(T=1.6 K)that could essentially differentiate various Fe-N_(4)states and invisible Fe-O species.By quantifying with CO-pulse chemisorption,site density and turnover frequency of Fe-N-C catalysts reach 2.4×10^(-9)site g^(-1)and 23 e site~(-1)s^(-1)during the ORR,respectively.Half-wave potential(0.915V_(RHE))of the Fe-N-C catalyst is more positive(approximately 54 mV)than that of Pt/C.Moreover,we observe that the performance of PEMFCs on Fe-N-C almost achieves the 2025 target of the US Department of Energy by demonstrating a current density of 1.037 A cm^(-2)combined with the peak power density of 0,685 W cm^(-2),suggesting the critical role of Fe(Ⅱ)-N_(4)site(D1).After 500 h of running,PEMFCs still deliver a power density of 1.26 W cm^(-2)at 1.0 bar H_(2)-O_(2),An unexpected rate-determining step is figured out by isotopic labelling experiment and theoretical calculation.This work not only offers valuable insights regarding the intrinsic contribution of Fe-N_(4)with a single spin state to alkaline/acidic ORR,but also provides great opportunities for developing high-performance stable PEMFCs.
基金Project supported by the National Natural Science Foundation of China(Nos.12332016,12172209,and 12202258)the Shanghai Gaofeng Project for University Academic Program Development。
文摘Traditional methods for measuring single-cell mechanical characteristics face several challenges,including lengthy measurement times,low throughput,and a requirement for advanced technical skills.To overcome these challenges,a novel machine learning(ML)approach is implemented based on the convolutional neural networks(CNNs),aiming at predicting cells'elastic modulus and constitutive equations from their deformations while passing through micro-constriction channels.In the present study,the computational fluid dynamics technology is used to generate a dataset within the range of the cell elastic modulus,incorporating three widely-used constitutive models that characterize the cellular mechanical behavior,i.e.,the Mooney-Rivlin(M-R),Neo-Hookean(N-H),and Kelvin-Voigt(K-V)models.Utilizing this dataset,a multi-input convolutional neural network(MI-CNN)algorithm is developed by incorporating cellular deformation data as well as the time and positional information.This approach accurately predicts the cell elastic modulus,with a coefficient of determination R^(2)of 0.999,a root mean square error of 0.218,and a mean absolute percentage error of 1.089%.The model consistently achieves high-precision predictions of the cellular elastic modulus with a maximum R^(2)of 0.99,even when the stochastic noise is added to the simulated data.One significant feature of the present model is that it has the ability to effectively classify the three types of constitutive equations we applied.The model accurately and reliably predicts single-cell mechanical properties,showcasing a robust ability to generalize.We demonstrate that incorporating deformation features at multiple time points can enhance the algorithm's accuracy and generalization.This algorithm presents a possibility for high-throughput,highly automated,real-time,and precise characterization of single-cell mechanical properties.
